Durvalumab with or without tremelimumab in combination with chemotherapy in first-line metastatic non-small-cell lung cancer: outcomes by tumor mutational burden in POSEIDON

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-05-01 DOI:10.1016/j.esmoop.2025.105058

S. Peters , K.S. Oliner , A. L’Hernault , M. Ratcliffe , H. Madison , Z. Lai , R. Stewart , H. Mann , C. Lowery , E.B. Garon , T. Mok , M.L. Johnson

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引用次数: 0

Abstract

Background

In updated analyses from the phase III POSEIDON study, after a median follow-up of >5 years, tremelimumab plus durvalumab and chemotherapy (T + D + CT) showed durable long-term overall survival (OS) benefit versus CT alone in first-line metastatic non-small-cell lung cancer (mNSCLC). In this article, we report the associations of tumor mutational burden (TMB) with outcomes of D with or without T in combination with CT versus CT alone.

Patients and methods

A total of 1013 patients with EGFR/ALK wild-type mNSCLC were randomized (1 : 1 : 1) to T + D + CT, D + CT, or CT, stratified by programmed cell death-ligand 1 (PD-L1) tumor cell (TC) expression ≥50% versus <50%, disease stage (IVA versus IVB) and histology (squamous versus nonsquamous). Patient subgroups were defined by a range of blood TMB (bTMB) values, including at a prespecified cut-off of 20 mutations (mut)/megabase (Mb) and across further subdivisions by PD-L1 TC expression ≥1% or <1% and by tissue TMB (tTMB) values.

Results

At the primary OS data cut-off (12 March 2021), at each bTMB or tTMB cut-off, the magnitude of OS benefit appeared greater among patients in the bTMB- or tTMB-high subgroups for the T + D + CT arm versus the CT arm but was similar between subgroups for the D + CT arm versus the CT arm. Updated OS analyses in the bTMB ≥20 and <20 mut/Mb subgroups, after median follow-up of >5 years (data cut-off 24 August 2023), were similar to those obtained at the primary OS data cut-off.

Conclusions

First-line treatment with T (limited course) plus D (until progression) and four cycles of CT consistently improved clinical outcomes versus CT alone in both bTMB-high and -low subgroups, and also in both high and low tTMB subgroups, in patients with mNSCLC. Benefit appeared greater in the TMB-high versus TMB-low subgroups; the addition of anti-cytotoxic T lymphocyte-associated antigen-4 to anti-PD-L1 and CT seemed to increase the magnitude of this difference.

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Durvalumab联合或不联合tremelimumab联合化疗治疗一线转移性非小细胞肺癌：POSEIDON肿瘤突变负担的结果

在III期POSEIDON研究的最新分析中，在中位随访5年后，tremelimumab + durvalumab和化疗（T + D + CT）在一线转移性非小细胞肺癌（mNSCLC）中显示出持久的长期总生存（OS）优于单独CT。在本文中，我们报告了肿瘤突变负担（TMB）与D联合或不联合T与单独CT的结果的关系。患者和方法共1013例EGFR/ALK野生型小细胞肺癌患者被随机（1:1:1）分为T + D + CT、D + CT或CT，按程序性细胞死亡配体1 （PD-L1）肿瘤细胞（TC）表达≥50% vs <；50%、疾病分期（IVA vs IVB）和组织学（鳞状vs非鳞状）分层。患者亚组由血液TMB （bTMB）值范围定义，包括预先指定的20个突变(mut)/兆基（Mb）的截止值，并通过PD-L1 TC表达≥1%或<；1%和组织TMB （tTMB）值进一步细分。结果：在主要OS数据截止日期（2021年3月12日），在每个bTMB或tTMB截止日期，T + D + CT组的bTMB或tTMB高亚组患者的OS获益幅度大于CT组，但D + CT组与CT组的亚组之间相似。在中位随访5年后（数据截止日期为2023年8月24日），bTMB≥20和<；20 mut/Mb亚组的最新OS分析与主要OS数据截止日期相似。结论：一线T（有限疗程）加D（直至进展）和4个周期CT治疗与单独CT治疗相比，在小细胞肺癌患者中，无论是高tTMB亚组还是低tTMB亚组，以及高tTMB亚组还是低tTMB亚组，均能持续改善临床结果。tmb -高亚组比tmb -低亚组获益更大；在抗pd - l1和CT中加入抗细胞毒性T淋巴细胞相关抗原-4似乎增加了这种差异的程度。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.